A Study of the Efficacy and Safety of Topiramate in the Prevention of Migraine

This is a randomized, double-blind, placebo-controlled, parallel-group, multi-center study to evaluate the effectiveness and safety of three different doses of topiramate (50mg, 100mg, and 200mg daily) in migraine prophylaxis. The study consists of five phases: baseline (determination of whether patients meet the eligibility criteria and tapering of any migraine medication patients are already taking); initial titration and double-blind phase (8 weeks) which begins with 25 mg/daily increasing to the assigned (50, 100, 200 mg/day topiramate); followed by a maintenance period at the target dose (18 weeks); tapering transition phase (up to 7 weeks); and open-label extension up to 6 months (to a maximum topiramate dose of 1600 mg/day); doses are adjusted to maximize effectiveness and minimize side effects. The primary study hypothesis is that one or more of the three doses of topiramate (50, 100, 200 mg/day) will be superior to placebo in the prophylaxis of migraine based on the change in monthly (28 day) migraine period rate from the prospective baseline period to the double-blind phase and that topiramate treatment is well tolerated. During the titration period (8 weeks), doses are increased to target dose of daily topiramate (50 milligrams[mg], 100, or 200mg) or placebo, taken twice daily by mouth. Doses are continued for 18 weeks, adjusted over 7 weeks, and continued for up to 6 months during the Open-Label Extension.

Inclusion criteria

• Medical history consistent with migraine with or without aura according to the International Headache Society (IHS) for at least 6 months prior to the study
• Between 3 to 12 migraine periods and no greater than 15 headache days (migraine and non-migraine) per month during the Baseline Phase
• No clinically significant abnormalities on neurological exams, electrocardiogram (ECG) or clinical laboratory test results at baseline
• Female patients must be postmenopausal for at least 1 year, surgically incapable of childbearing, practicing abstinence, or practicing an acceptable method of contraception (requires negative pregnancy test)

Exclusion criteria

• Patients with headaches other than migraine
• Patients with episodic tension or sinus headaches
• Onset of migraine after age of 50 years
• Patients who have failed more than two adequate regimens for migraine prophylaxis
• Patients who overuse pain medications or certain other medications